Clinical Outcomes in Patients Aged 80 Years or Older Receiving Non-Invasive Respiratory Support for Hypoxemic Acute Respiratory Failure Consequent to COVID-19

: As the clinical outcome of octogenarian patients hospitalised for COVID-19 is very poor, here we assessed the clinical characteristics and outcomes of patients aged 80 year or older hospitalised for COVID-19 receiving non-invasive respiratory support (NIRS). A multicentre, retrospective, observational study was conducted in seven hospitals in Northern Italy. All patients aged ≥80 years with COVID-19 associated hypoxemic acute respiratory failure (hARF) undergoing NIRS between 24 February 2020, and 31 March 2021, were included. Out of 252 study participants, 156 (61.9%) and 163 (64.6%) died during hospital stay and within 90 days from hospital admission, respectively. In this case, 228 (90.5%) patients only received NIRS (NIRS group), while 24 (9.5%) were treated with invasive mechanical ventilation (IMV) after NIRS failure (NIRS+IMV group). In-hospital mortality did not significantly differ between NIRS and NIRS+IMV group (61.0% vs. 70.8%, respectively; p = 0.507), while survival probability at 90 days was significantly higher for NIRS compared to NIRS+IMV patients (0.379 vs. 0.147; p = 0.0025). The outcome of octogenarian patients with COVID-19 receiving NIRS is quite poor. Caution should be used when considering transition from NIRS to IMV after NIRS failure

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic–clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic–clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed

Modelling, Design and Fabrication of Interdigitated Electrode Sensors for Biomedical Applications

In microphysiological systems different signal parameters as changes in the extracellular acidification, ion concentration, and membrane potential can be easily measured with integrated microsensors. The rising interest to perform, in such microsystems, impedance measurements by means of large area interdigitated microelectrodes array, is justified by their potential use to control the cellular adhesion and for a real-time monitoring of the cell physiological state. Variations on the cell density, growth and long term cellular behaviour can be easily evaluated by monitoring the change on the electrode impedance. Recently, nanoscaled interdigitated electrode array have been also employed to detect the affinity binding of certain DNA molecules. Although the scaling of the applied electrode configuration dimensions is often compatible with modern planar sensor technologies, precise design criteria must be however introduced in order to increase the sensor and the signal processing electronic performances: the geometrical dimensions, the choice of the electrode material and the interface electrochemistry are some of the parameters to be considered when optimising new designs. In this work a simple model has been implemented in SPICE to study the effects of both the electrochemical and geometrical parameters of interdigitated microelectrode sensors (IDES) ranging over the biomedical and biotechnological application areas. Starting from previous analytical studies, based on the conformal mapping method, the core of the implemented model consists on a two-electrode conductivity cell where the double layer, the parasitic and the solution effects have been considered. With an interactive procedure the model has been extended to more electrode configurations. In order to validate the simulation results two approach have been pursued: firstly, some indications about the calculated IDES electrical parameters, as the electric potential and field distribution have been obtained with ANSYS by finite element method based simulations. Lastly, planar microelectrode test structures with different characteristics have been realised and the impedance spectroscopy measurements have been compared with the simulation result

Vertically structured thin membranes by a lost mold technique

For MEMS applications it will be more and more important to fabricate thin membranes with low intrinsic stress while maintaining high mechanical and structural performance in terms of rigidity and resilience. In this paper a new approach to obtain stiff thin membranes is presented as an alternative to conventional membranes obtained by bulk micromaching methods (like chemical or electro-chemical etch stop technique). The reinforcement of the membranes is achieved by vertical structures obtained by filling a mold of deeply etched silicon trenches with different materials (SiO2, Si3N4, polysilicon) and subsequent removal of the bulk silicon. The theoretical estimation of the rigidity of a plate with vertical enforcement strips has been studied by the comparison of the inertial modulus of beams with T-shaped section. The mechanical behavior of membranes stiffened by vertical structures with different dimensions (in terms of depth, thickness and pitch) has been investigated through simulation using ANSYS as finite elements analysis software. The silicon trenches have been fabricated by deep reactive ion etching (DRIE) based on SF6/O2 plasma, using a 500 nm thick TEOS as masking layer. These structures have been subsequently sealed by deposition of a silicon oxide layer and filled by poly-silicon. The silicon oxide has been used both to calibrate the trench dimensions and as etch-stop layer for the TMAH anisotropic etch that is required to release the three dimensional structure. For this reason, some experiments have been carried out to define the best conformality condition in terms of thickness uniformity of the layer between different type of silicon oxide (thermal oxide, TEOS, LTO). In order to minimise the intrinsic stress distribution due to the deposition process and to optimise the polysilicon conformality, the effects of the annealing temperature and the boron doping conditions have been characterised. The mechanical behaviour of these structures has been measured under different load conditions

Optimization of TMAH etching for MEMS

Tetra-methyl ammonium hydroxide (TMAH) is an anisotropic silicon etchant that is gaining considerable use in silicon sensor micromachining due to its excellent compatibility with CMOS processing, selectivity, anisotropy and relatively low toxicity, as compared to the more used KOH and EDP etchants. In this paper, the influence of temperature and concentration of the TMAH solution together with oxidizer additions is studied in order to optimize the anisotropic silicon etching for MEMS fabrication. In particular this optimized etchant formulation has been employed ad ITC-Irst in the development of a basic fabrication process for piezoresistive pressure sensors based on a silicon membrane and four resistors connected in a Weathstone bridge configuration. The active element of the sensor, i.e. the thin silicon membrane, is formed by etching anisotropically from the backside of the wafer. Both process and etchin have to be tuned and matched in order to obtain an optimum fabrication sequence. Some improvements such as higher etch rate and better surface finish have been obtained by the addition of ammonium peroxidisulfate as oxidizing agent under different conditions. This simplifies both the post processing and the etch set-up. The process parameters and the thermo-electro-mechanincal characteristics of the pressure sensors (as piezoresistors resistivity, device sensibility, temperature coefficients. membrane thickness) were tested and are compared with the analytical and numerical simulations (ANSYS, ISE-TCAD)

Antiseizure Medications in Alzheimer’s Disease from Preclinical to Clinical Evidence

Alzheimer’s disease (AD) and epilepsy are common neurological disorders in the elderly. A bi-directional link between these neurological diseases has been reported, with patients with either condition carrying almost a two-fold risk of contracting the other compared to healthy subjects. AD/epilepsy adversely affects patients’ quality of life and represents a severe public health problem. Thus, identifying the relationship between epilepsy and AD represents an ongoing challenge and continuing need. Seizures in AD patients are often unrecognized because they are often nonconvulsive and sometimes mimic some behavioral symptoms of AD. Regarding this, it has been hypothesized that epileptogenesis and neurodegeneration share common underlying mechanisms. Targeted treatment to decrease epileptiform activity could represent a valuable strategy for delaying the neurodegenerative process and related cognitive impairment. Several preclinical studies have shown that some antiseizure medications (ASMs) targeting abnormal network hyperexcitability may change the natural progression of AD. However, to date, no guidelines are available for managing seizures in AD patients because of the paucity of randomized clinical trials sufficient for answering the correlated questions. Future AD clinical studies are mandatory to update clinicians about the symptomatic treatment of seizures in AD patients and recognize whether ASM therapy could change the natural progression of the disease, thereby rescuing cognitive performance

Feasibility study on fabrication of piezoresistive pressure sensors using silicon micromachining technology

This paper describes a feasibility study on design and fabrication of piezoresistive pressure sensors for the pressure range 0.5 - 350 bar, using silicon micromachining technology. Different technological steps are studied in order to optimize the fabrication process and the electro-mechanical parameters of the device. The sensing membrane is etched in (100)-oriented silicon by anisotropic etching using different concentration of TMAH (tetramethyl anmmnium hydroxide) in water solution. The software package ISE-TCAD. based on the finite element method (FEM), has been used to calculate the stress distribution on the membrane in order to provide information for the proper location of the piezoresistors.Devices with different membrane thickness (between 120 and 40 um) have been investigated. All devices show a good linearity (better than 1%) and their sensibility ranges from 3 to 58 mV/Vbar depending on the membrane thickness

Plasma total and unacylated ghrelin predict 5-year changes in insulin resistance

Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UG) forms, and higher plasma total ghrelin (TG) and UG may be cross-sectionally associated with lower insulin resistance in metabolic syndrome patients. The potential value of ghrelin forms in predicting insulin resistance and its time-related changes in community-based population cohorts remains unknown